New Coronavirus (SARS-CoV-2)

Discharge criteria for confirmed COVID-19 cases: When is it safe to discharge COVID-19 cases from the hospital or end home isolation?

This document has been produced at the request of an EU / EEA Member State. It suggests criteria to consider when deciding whether a confirmed case of COVID-19 can be safely discharged (i.e., without being infectious) from the hospital or discharged from home isolation.

To address this request, the following working questions were developed:

  • What is the duration of shedding of the SARS-CoV-2 virus in the body fluids of symptomatic patients after remission of symptoms?
  • What is the duration of shedding of the SARS-CoV-2 virus in body fluids of asymptomatic patients?
  • What tests are available to document lack of infectivity in a previously diagnosed infection?
  • What is the longest documented transmission of an asymptomatic person?

The ECDC then provides a desk review of existing guidance documents and protocols from national and international organizations and a convenient search for peer-reviewed publications.

What is the duration of shedding of the SARS-CoV-2 virus in the body fluids of symptomatic patients after remission of symptoms?

The SARS-CoV-2 virus can be initially detected 1–2 days before the onset of symptoms in samples from the upper respiratory tract; the virus can persist for 7 to 12 days in moderate cases and up to 2 weeks in severe cases (report of the WHO mission to China) [1]. In feces, viral RNA was detected in up to 30% of patients from day 5 after onset and up to 4 to 5 weeks in moderate cases. The importance of fecal viral shedding for transmission remains to be clarified [1].

Prolonged viral shedding of nasopharyngeal aspirates, up to at least 24 days after onset of symptoms, has been reported among COVID-19 patients in Singapore [2]. Researchers from Germany also reported prolonged viral shedding with high sputum viral load after recovery in a convalescent patient [3]. However, they acknowledge that the viability of SARS-CoV-2 detected by qRT-PCR in this patient has not been proven by viral culture.

Prolonged shedding of the virus has been observed in convalescent children after mild infections, in samples of the respiratory tract (22 days) and stool (between two weeks and more than one month) [4].

A shift from positive oral swab samples during early infection to positive rectal swab samples during late infection was observed in Chinese patients; The authors expressed concern that COVID-19 patients were discharged from the hospital on the basis of negative oral swabs [5].

Researchers from China report that in samples from the upper respiratory tract, the shedding pattern of viral nucleic acid in patients infected with SARS-CoV-2 resembles that of patients with influenza; It also appears to be different from the pattern seen in patients infected with SARS-CoV-1 [6]. ECDC Comment: Although the oral-fecal route does not appear to be a transmission factor, its significance has yet to be determined. Discharged patients should be advised to strictly follow personal hygiene precautions to protect household contacts. This applies to all convalescent patients, but particularly to convalescent children.

What is the duration of the shedding of the SARS-CoV-2 virus in the body fluids of asymptomatic patients?

The virus has been detected in asymptomatic people. Pan et al. reports of a family group where a mother and child were asymptomatic but had positive RT-PCR results [7]. Hoehl et al. (2020) also report that two of the 114 Germans who were evacuated from Hubei province on February 1, 2020, tested positive in two throat swab samples by RT-PCR and were asymptomatic [8]. The two people were isolated in a hospital in Frankfurt, where a mild skin rash and minimal pharyngitis were observed in one of them. Both patients were still well and afebrile 7 days after admission. The potential infectivity was confirmed by virus culture.

Zou et al. 2020 report that the viral load of asymptomatic patients was similar to that of symptomatic patients, indicating a potential for transmission from asymptomatic or pre-symptomatic patients [6]. The study reports that patients with few or no symptoms had modest levels of detectable viral RNA in the oropharynx for at least 5 days [6].

Potential transmission from asymptomatic people has been reported. Bai et al. 2020 reports a family group of five hospitalized COVID-19 patients with fever and respiratory symptoms who had contact before the onset of symptoms with an asymptomatic relative, a 20-year-old young woman, after their return from Wuhan. She remained asymptomatic for the entire duration of clinical and laboratory monitoring (19 days) [9]. ECDC comment: Provided there are sufficient resources, there is a clear benefit to evaluating asymptomatic patients before they are released from isolation. However, in the context of limited resources for healthcare and laboratories during the COVID-19 epidemic, the evaluation of symptomatic individuals should take priority over the evaluation of asymptomatic patients prior to release from isolation.

What tests are available to document lack of infectivity in a previously diagnosed infection?

On its website, the ECDC provides the following tips. The specific tests currently recommended by WHO for the diagnosis and confirmation of SARS-CoV-2 are described on a dedicated WHO web page. Una prueba positiva única debe confirmarse mediante un segundo ensayo de RT-PCR dirigido a un gen diferente de SARS-CoV-2. A single negative test for SARS-CoV-2 (especially if it comes from an upper respiratory tract sample) or a positive test result for another respiratory pathogen result does not exclude SARS-CoV-2 infection.

A high RT-PCR cycle threshold value (eg> 35) obtained as a result of the E gene RT-PCR could be due to contamination of the reagents by the E gene positive control In countries where the epidemic is still not widespread, all positive results must be confirmed with a second genetic endpoint. In countries with a generalized epidemic, a genetic target is considered sufficient (see the updated WHO laboratory guide). However, confirmation of positive test results that have high CT values still needs to be considered in all regions and countries.

What is the longest documented transmission of an asymptomatic person?

There is insufficient evidence to provide a qualified answer to this question.

Importance of the persistence of viral RNA against infectious virus?

Viral RNA can persist for long periods of time in body fluids. This does not necessarily mean that the person is still infectious. Isolation of virus in virus culture is necessary to show infectivity of the virus. Hoehn et al. 2020 reported infectious viruses from two asymptomatic cases [8].

The following table provides an overview of the recommendations for de-isolation of COVID-19 patients from national agencies in countries that have experienced local SARS-CoV-2 transmissions.

Despite some differences in practice, there is a consensus to combine a) evidence of viral RNA clearance from the upper respiratory tract with b) clinical resolution of symptoms.

At least two SARS-CoV-2 negative upper respiratory tract specimens, collected at intervals of ≥ 24 hours, are recommended to document clearance of SARS-CoV-2.

  • For symptomatic patients after resolution of symptoms, specimens should be collected at least seven days after onset or after> 3 days without fever.
  • For asymptomatic people infected with SARS-CoV-2, tests to document virus shedding should be taken at least 14 days after the initial positive test.
  • Italy indicates that serological tests to document specific IgG antibodies to SARS-CoV-2 will be valuable

Table: Comparison of current guidelines on de-isolation of COVID-19 cases:

Symptomatic cases, hospitalized.Asymptomatic infections, isolated people at home.
Ministry of Health, Superior Council of Health, Italy (February 28, 2020)A COVID-19 patient can be considered cured after resolution of symptoms and 2 negative tests for SARS-CoV-2 at 24 hour intervals.

For patients who recover clinically before 7 days after initiation, an interval of 7 days between the first and the final test is recommended.

Note: Virus shedding is defined as the disappearance of viral RNA from the body fluids of symptomatic and asymptomatic people, accompanied by the appearance of specific IgG.
SARS-CoV-2 RNA test negative at 14 days after the first test (end of the quarantine period).
China CDC
Diagnostic and Treatment Protocol for COVID-19 Patients (Trial Version 7, Revised)
Patients who meet the following criteria can be discharged:

* Afebrile for> 3 days, improved respiratory symptoms,
* The lung image shows obvious absorption of inflammation, and
* Nucleic acid tests are negative for the respiratory tract pathogen two consecutive times (sampling interval ≥ 24 hours).

After discharge, patients are advised to continue 14 days of isolation management and health monitoring, wear a mask, live in a single room with good ventilation, reduce close contact with family members, eat separately , keep your hands clean and avoid outdoor activities.

It is recommended that discharged patients have follow-up visits after 2 and 4 weeks.
National Center for Infectious Diseases (NCID) Singapore
De-isolation of suspected COVID-19 cases:
Discharge the patient with advice and clinical monitoring if indicated and with daily wellness calls until day 14 after the last possible exposure, under the following conditions:

Afebril ≥ 24 hours,
* 2 respiratory samples with a negative result for SARS-CoV-2 by PCR in ≥ 24 hours,
* Day of illness from onset ≥ 6 days.
Or
Alternative etiology found (eg, Influenza, bacteremia)
Or
* Not a close contact of a COVID-19 case
* Does not require hospital care for other reasons.
CDC USA
Interim Guidance for Discontinuation of Transmission-Based Precautions and Disposal of Hospitalized COVID-19 Patients:
Negative rRT-PCR results from at least 2 consecutive series of nasopharyngeal and throat swabs collected ≥ 24 hours from a COVID-19 patient (a total of four negative samples) AND resolution of fever, without the use of antipyretic medications , improvement in the signs and symptoms of the disease.

Note: The decision must be made on a case-by-case basis in consultation with physicians and public health officials.
CDC USA
Interim Guidance for Breaking Home Isolation for COVID-19 Patients:
At least 2 consecutive series of nasopharyngeal and throat swabs collected ≥ 24 hours from a COVID-19 patient (a total of four negative samples).

And resolution of the fever, without the use of antipyretic drugs, improves the signs and symptoms of the disease.

Note: The decision should be made on a case-by-case basis in consultation with physicians and public health officials.

References

1. World Health Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). Geneva: WHO; 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf.

2. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020.

3. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C, et al. Transmission of 2019-nCoV Infection from an asymptomatic contact in Germany. New England Journal of Medicine. 2020;382(10):970-1.

4. Cai J, Xu J, Lin D, Yang z, Xu L, Qu Z, et al. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clinical Infectious Diseases. 2020.

5. Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections. 2020 2020/01/01;9(1):386-9.

6. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral load in upper respiratory specimens of infected patients. New England Journal of Medicine. 2020.

7. Pan X, Chen D, Xia Y, Wu X, Li T, Ou X, et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. The Lancet Infectious Diseases. 2020 2020/02/19/.

8. Hoehl S, Rabenau H, Berger A, Kortenbusch M, Cinatl J, Bojkova D, et al. Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China. New England Journal of Medicine. 2020.

9. Bai Y, Yao L, Wei T, Tian F, Jin D-Y, Chen L, et al. Presumed Asymptomatic carrier transmission of COVID-19. JAMA. 2020.

Source: https://www.ecdc.europa.eu/en

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